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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Design and analysis of synthetic carbon fixation pathways
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Design and analysis of synthetic carbon fixation pathways

机译：合成碳固定路径的设计和分析

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Carbon fixation is the process by which CO_2 is incorporated into organic compounds. In modern agriculture in which water, light, and nutrients can be abundant, carbon fixation could become a significant growth-limiting factor. Hence, increasing the fixation rate is of major importance in the road toward sustainability in food and energy production. There have been recent attempts to improve the rate and specificity of Rubisco, the carboxylating enzyme operating in the Calvin-Benson cycle; however, they have achieved only limited success. Nature employs several alternative carbon fixation pathways, which prompted us to ask whether more efficient novel synthetic cycles could be devised. Using the entire repertoire of approximately 5,000 metabolic enzymes known to occur in nature, we computationally identified alternative carbon fixation pathways that combine existing metabolic building blocks from various organisms. We compared the natural and synthetic pathways based on physicochemical criteria that include kinetics, energetics, and topology. Our study suggests that some of the proposed synthetic pathways could have significant quantitative advantages over their natural counterparts, such as the overall kinetic rate. One such cycle, which is predicted to be two to three times faster than the Calvin-Benson cycle, employs the most effective carboxylating enzyme, phosphoenolpyruvate carboxylase, using the core of the naturally evolved C4 cycle. Although implementing such alternative cycles presents daunting challenges related to expression levels, activity, stability, localization, and regulation, we believe our findings suggest exciting avenues of exploration in the grand challenge of enhancing food and renewable fuel production via metabolic engineering and synthetic biology.
机译：碳固定是将CO_2掺入有机化合物的过程。在水，光和营养丰富的现代农业中，固碳可能成为重要的增长限制因素。因此，提高固着率对于实现食品和能源生产的可持续性至关重要。最近有尝试改善在Calvin-Benson循环中运作的羧化酶Rubisco的速率和特异性。但是，他们仅取得了有限的成功。大自然采用了几种替代性的碳固定途径，这促使我们问是否可以设计出更有效的新型合成循环。利用已知自然界中约5,000种代谢酶的全部组成，我们通过计算确定了替代碳固定途径，该途径结合了来自各种生物体的现有代谢构件。我们根据物理化学标准（包括动力学，能量学和拓扑结构）比较了天然和合成途径。我们的研究表明，某些拟议的合成途径可能比天然途径具有明显的数量优势，例如总体动力学速率。一个这样的循环，预计比Calvin-Benson循环快2至3倍，它利用最有效的羧化酶，磷酸烯醇丙酮酸羧化酶，利用自然进化的C4循环的核心。尽管实施这样的替代性循环提出了与表达水平，活性，稳定性，本地化和调控有关的艰巨挑战，但我们相信我们的发现为通过代谢工程和合成生物学增强食品和可再生燃料生产的巨大挑战提供了令人兴奋的探索途径。

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